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The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 phenotype by keratin 16.

Paladini RD, Coulombe PA - J. Cell Biol. (1999)

Bottom Line: Degenstein, E.Fuchs. 1995.Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
The type I epidermal keratins K14 and K16 are remarkably similar at the primary sequence level. While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia. To compare directly the functions of the two keratins we have targeted the expression of the human K16 cDNA to the progenitor basal layer of the epidermis of K14 mice. Mice for K14 blister extensively and die approximately 2 d after birth (Lloyd, C., Q.C. Yu, J. Cheng, K. Turksen, L. Degenstein, E. Hutton, and E. Fuchs. 1995. J. Cell Biol. 129:1329-1344). The skin of mice expressing K16 in the absence of K14 developed normally without evidence of blistering. However, as the mice aged they featured extensive alopecia, chronic epidermal ulcers in areas of frequent physical contact, and alterations in other stratified epithelia. Mice expressing a control K16-C14 cDNA also rescue the blistering phenotype of the K14 mice with only a small percentage exhibiting minor alopecia. While K16 is capable of rescuing the blistering, phenotypic complementation in the resulting skin is incomplete due to the multiple age dependent anomalies. Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

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Transmission electron microscopy of wild-type and replacement mouse epidermis. Ventral skin was isolated from 7-d-old wild-type and K16 replacement mice and processed for electron microscopy. (A and B) Basal cells from wild-type (A) and K16 replacement epidermis (B). K16 replacement basal keratinocytes (B) are morphologically similar to wild-type keratinocytes (A). Both feature bundles of filaments (kf) distributed throughout the cytoplasm and multiple desmosomal (small arrowheads) and hemidesmosomal (arrows) attachments. There is no evidence of decreased cell-cell adhesion or blistering in any layers of the epidermis. Large arrowheads, the basal lamina. Nu, nucleus; m, mitochondria. Bar: (A and B) 2 μm.
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Figure 2: Transmission electron microscopy of wild-type and replacement mouse epidermis. Ventral skin was isolated from 7-d-old wild-type and K16 replacement mice and processed for electron microscopy. (A and B) Basal cells from wild-type (A) and K16 replacement epidermis (B). K16 replacement basal keratinocytes (B) are morphologically similar to wild-type keratinocytes (A). Both feature bundles of filaments (kf) distributed throughout the cytoplasm and multiple desmosomal (small arrowheads) and hemidesmosomal (arrows) attachments. There is no evidence of decreased cell-cell adhesion or blistering in any layers of the epidermis. Large arrowheads, the basal lamina. Nu, nucleus; m, mitochondria. Bar: (A and B) 2 μm.

Mentions: To finely assess whether young replacement epidermis was truly similar to wild-type epidermis, ventral skin from 7-d-old wild-type and K16 replacement mice was examined by transmission electron microscopy. There were no discernible morphological differences between replacement and wild-type basal keratinocytes. K16 replacement basal keratinocytes (Fig. 2 B) had a low-columnar, cuboidal shape and were tightly packed together. There were no obvious alterations in cell-cell or cell-matrix adhesion. Keratin filaments were loosely bundles and distributed throughout the cytoplasm. These same morphological characteristics were observed in both wild-type (Fig. 2 A) and K16-C14 replacement basal keratinocytes (data not shown). There was also no evidence of cell lysis or epidermal blistering. Spinous keratinocytes in the replacement epidermis (K16 or K16-C14) were also normal. Filament bundling occurred with the concomitant increase in the number of desmosomes (data not shown). Cells in the granular layer and the stratum corneum of replacement epidermis were also similar to wild-type (data not shown). By all morphological criteria, the replacement epidermides are equivalent to wild-type epidermis. This is in stark contrast to what was observed in the basal keratinocytes from ectopic K16 phenotypic epidermis in which the hypertrophic basal keratinocytes had large aggregations of keratin filaments and major decreases in cell-cell adhesion 39.


The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 phenotype by keratin 16.

Paladini RD, Coulombe PA - J. Cell Biol. (1999)

Transmission electron microscopy of wild-type and replacement mouse epidermis. Ventral skin was isolated from 7-d-old wild-type and K16 replacement mice and processed for electron microscopy. (A and B) Basal cells from wild-type (A) and K16 replacement epidermis (B). K16 replacement basal keratinocytes (B) are morphologically similar to wild-type keratinocytes (A). Both feature bundles of filaments (kf) distributed throughout the cytoplasm and multiple desmosomal (small arrowheads) and hemidesmosomal (arrows) attachments. There is no evidence of decreased cell-cell adhesion or blistering in any layers of the epidermis. Large arrowheads, the basal lamina. Nu, nucleus; m, mitochondria. Bar: (A and B) 2 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2169494&req=5

Figure 2: Transmission electron microscopy of wild-type and replacement mouse epidermis. Ventral skin was isolated from 7-d-old wild-type and K16 replacement mice and processed for electron microscopy. (A and B) Basal cells from wild-type (A) and K16 replacement epidermis (B). K16 replacement basal keratinocytes (B) are morphologically similar to wild-type keratinocytes (A). Both feature bundles of filaments (kf) distributed throughout the cytoplasm and multiple desmosomal (small arrowheads) and hemidesmosomal (arrows) attachments. There is no evidence of decreased cell-cell adhesion or blistering in any layers of the epidermis. Large arrowheads, the basal lamina. Nu, nucleus; m, mitochondria. Bar: (A and B) 2 μm.
Mentions: To finely assess whether young replacement epidermis was truly similar to wild-type epidermis, ventral skin from 7-d-old wild-type and K16 replacement mice was examined by transmission electron microscopy. There were no discernible morphological differences between replacement and wild-type basal keratinocytes. K16 replacement basal keratinocytes (Fig. 2 B) had a low-columnar, cuboidal shape and were tightly packed together. There were no obvious alterations in cell-cell or cell-matrix adhesion. Keratin filaments were loosely bundles and distributed throughout the cytoplasm. These same morphological characteristics were observed in both wild-type (Fig. 2 A) and K16-C14 replacement basal keratinocytes (data not shown). There was also no evidence of cell lysis or epidermal blistering. Spinous keratinocytes in the replacement epidermis (K16 or K16-C14) were also normal. Filament bundling occurred with the concomitant increase in the number of desmosomes (data not shown). Cells in the granular layer and the stratum corneum of replacement epidermis were also similar to wild-type (data not shown). By all morphological criteria, the replacement epidermides are equivalent to wild-type epidermis. This is in stark contrast to what was observed in the basal keratinocytes from ectopic K16 phenotypic epidermis in which the hypertrophic basal keratinocytes had large aggregations of keratin filaments and major decreases in cell-cell adhesion 39.

Bottom Line: Degenstein, E.Fuchs. 1995.Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
The type I epidermal keratins K14 and K16 are remarkably similar at the primary sequence level. While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia. To compare directly the functions of the two keratins we have targeted the expression of the human K16 cDNA to the progenitor basal layer of the epidermis of K14 mice. Mice for K14 blister extensively and die approximately 2 d after birth (Lloyd, C., Q.C. Yu, J. Cheng, K. Turksen, L. Degenstein, E. Hutton, and E. Fuchs. 1995. J. Cell Biol. 129:1329-1344). The skin of mice expressing K16 in the absence of K14 developed normally without evidence of blistering. However, as the mice aged they featured extensive alopecia, chronic epidermal ulcers in areas of frequent physical contact, and alterations in other stratified epithelia. Mice expressing a control K16-C14 cDNA also rescue the blistering phenotype of the K14 mice with only a small percentage exhibiting minor alopecia. While K16 is capable of rescuing the blistering, phenotypic complementation in the resulting skin is incomplete due to the multiple age dependent anomalies. Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

Show MeSH
Related in: MedlinePlus